Cesium carbonate → Tert-butyl 4-(2-(7-(2-methoxyethoxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl)piperazine-1-carboxylate

HRID 339666Notes

Reaction equation

HRID 339666 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[C:14]([C:17]1[N:21]3[CH:22]=[CH:23][C:24]([O:26][CH2:27][CH2:28][O:29][CH3:30])=[CH:25][C:20]3=[N:19][N:18]=1)[CH:13]=[CH:12]2)(=O)=O.[N:33]1([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:30][O:29][CH2:28][CH2:27][O:26][C:24]1[CH:23]=[CH:22][N:21]2[C:17]([C:14]3[CH:13]=[CH:12][C:11]4[C:16](=[C:7]([N:36]5[CH2:35][CH2:34][N:33]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:38][CH2:37]5)[CH:8]=[CH:9][CH:10]=4)[N:15]=3)=[N:18][N:19]=[C:20]2[CH:25]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 866543412-(7-(2-Methoxyethoxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl trifluoromethane sulfonate

Product 1

HCID 67234014Tert-butyl 4-(2-(7-(2-methoxyethoxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl)piperazine-1-carboxylateYield 76%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

2-(7-(2-methoxyethoxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl trifluoromethane sulfonate (0.027 g, 0.0576 mmol), tert-butyl piperazine-1-carboxylate (0.0215 g, 0.115 mmol), Cs2CO3 (0.0282 g, 0.0865 mmol), Pd2dba3 (0.00528 g, 0.00576 mmol) and Binap-rac (0.00718 g, 0.0115 mmol) were combined in toluene (0.5 mL) in a sealed vial. The reaction mixture was stirred at 100° C. for 16 hours then concentrated under reduced pressure. The resulting residue was diluted with EtOAc, washed with aqueous saturated NaHCO3 and brine, dried over Na2SO4, filtered and concentrated under reduced pressure to an orange solid. Purification via flash column chromatography (40:1 DCM/MeOH followed by 20:1 DCM/MeOH) provided 22 mg (76%) of desired product.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. additionThe resulting residue was diluted with EtOAc
  3. washwashed with aqueous saturated NaHCO3 and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure to an orange solid
  7. customPurification via flash column chromatography (40:1 DCM/MeOH followed by 20:1 DCM/MeOH)

Sources & evidence

ORD record
ord-eae17a99922f46e996183ebca4aa75cd
Source dataset
uspto-grants-2014_11
Patent number
US08895550B2

Reaction notes

Loading…